The safety and efficacy of everolimus for the treatment of progressive gastroenteropancreatic neuroendocrine tumors: A multi-institution observational study in Taiwan

[[abstract]]Renoprotective effect of combining pentoxifylline with renin-angiotensin-aldosterone system blockade in pre-dialyzed advanced chronic kidney disease patients - a ntionwide database analysis. Objective: Everolimus is an inhibitor of the mammalian target of rapamycin. It has been approved for patients with advanced pancreatic neuroendocrine tumors (NETs) since 2011. This study aimed to evaluate the safety and efficacy of everolimus in Taiwanese patients with progressive, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods: Forty-six patients with progressive, advanced GEP-NETs who received everolimus treatment between January 2008 and August 2014 at six medical centers across Taiwan were selected. Patient’s characteristics, tumor features, safety profiles and treatment efficacy with everolimus were retrospectively analyzed from medical charts. Results: The median follow up duration was 20.1 (range 1.2–67.6) months and 35 of 46 patients (76.1%) remained alive at the end of study. The 1- and 2-year overall survival rates were 91.3% and 71.7%, respectively. The median progression free survival (PFS) was 17.0 (range 6.8–27.1) months. Regarding the best response of everolimus treatment, 11 (19.0%) patients had partial response, 27 (46.6%) patients had stable disease and 8 (13.8%) patients had progressive disease. Patients with World Health Organization (WHO) grade 1 NETs, nonfunctional tumor, not use of somatostatin analogue and use only one targeting agent everolimus rather than two lines of targeting agent or more had significant better PFS under everolimus treatment. The most common adverse events associated with everolimus were stomatitis (31.1%), rash (22.2%), and hyperglycemia (17.1%). Seven (15.4%) patients experienced severe adverse events (grade III or more). Grade III adverse events included hyperglycemia (4.4%), anemia (4.4%), fatigue (2.2%), and elevated liver function test (2.2%).One (2.2%) patient death due to grade V interstitial pneumonitis. Conclusions: Everolimus was an effective treatment option for Taiwanese patients with progressive, advanced GEP NETs. Clinicians must be aware of and able to manage common adverse events to maximize patient compliance with everolimus